The Lens and Cataract Biology Section studies the mechanisms of cataractogenesis and works to develop potential anti-cataract therapies. A compound (TEMPOL-H) previously shown to have anti-cataract activity in a lens organ culture screening system has been licensed for development and initial clinical testing is anticipated shortly. The lens organ culture system is being used to probe several aspects of lens biology. Dr. Rachel Neal is comparing the deleterious effects of lead exposure on the lens in this system with earlier data obtained in live animals. Lead exposure in vitro alters lens histology, predisposes the lens to cataract development, and alters the protein expression profiles within the lens. Dr. Madhumita Ghosh has begun to address basic questions concerning lens cell proliferation and differentiation in the organ cultured lens. In both studies, a proteomics approach is being used to identify and quantify changes in protein expression and protein modifications that occur in the lens in response to stress (i.e. lead exposure) or other changes in environmental conditions. The hydration properties of the lens are crucial to the maintenance of lens transparency. Syneresis, the release of water from the hydration layers of proteins, is a factor in age-related cataractogenesis. Dr. Fred Bettelheim has used NMR relaxographic studies on intact human lenses to analyze the movement of water into and out of the hydration layer. As a function of age the amount of bound water decreases throughout all regions of the lens. These studies also demonstrated that in response to changes in hydrostatic pressure the lens can reversibly move water into or out of the hydration layer to counteract the associated osmotic pressure change. This reversible syneretic response is most prominent in the lens cortex and diminishes with age. The results suggest that both cataract and presbyopia may have syneretic components in their etiology.